In order to elucidate neurochemical alterations associated with defective brain development, the influence of experimental cretinism on the metabolism and deposition of biogenic monamines in the rat central nervous system is being investigated. The developmental patterns of dopamine, nerepinephrine and serotonin in discrete brain regions (brain stem, basal ganglia, hypothalamus) of normal rats will be compared with those in cretinous animals and in rats with neonatal hyperthyroidism. The ability of thyroid hormone replacement therapy, initiated at various ages after birth, to correct the abnormal ontogenic patterns of these amines in the brains of cretinous rats will be studied. It is proposed to investigate the mechanisms responsible for abnormal brain amine levels in cretinous rats. The turnover rates of dopamine, norepinephrine and serotonin will be compared in cretinous rats and their control littermates. The effect of cretinism on the activities of brain enzymes involved in monoamine synthesis (tyrosine hydroxylase, tryptophan hydroxylase) and degradation (monoamine oxidase, catechol-o-methyl transferase) will be studied. Cretinism-induced alterations in the synaptosomal uptake of dopamine, norepinephrine and serotonin will also be examined.